Nucleic acid vaccines have shown promising potency and efficacy for cancer treatment with robust and specific T-cell responses. Improving the immunogenicity of delivered antigens helps to extend therapeutic efficacy and reduce dose-dependent toxicity. Here, we systematically evaluated chemokine-fused HPV16 E6/E7 antigen to improve the cellular and humoral immune responses induced by nucleotide vaccines in vivo. We found that fusion with different chemokines shifted the nature of the immune response against the antigens. Although a number of chemokines were able to amplify specific CD8 + T-cell or humoral response alone or simultaneously. CCL11 was identified as the most potent chemokine in improving immunogenicity, promoting specific CD8 + T-cell stemness and generating tumor rejection. Fusing CCL11 with E6/E7 antigen as a therapeutic DNA vaccine significantly improved treatment effectiveness and caused eradication of established large tumors in 92% tumor-bearing mice (n = 25). Fusion antigens with CCL11 expanded the TCR diversity of specific T cells and induced the infiltration of activated specific T cells, neutrophils, macrophages and dendritic cells (DCs) into the tumor, which created a comprehensive immune microenvironment lethal to tumor. Combination of the DNA vaccine with anti-CTLA4 treatment further enhanced the therapeutic effect. In addition, CCL11 could also be used for mRNA vaccine design. To summarize, CCL11 might be a potent T cell enhancer against cancer.

中文翻译：

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CCL11 与抗原的基因融合增强了核酸疫苗的抗原性，并通过优化 T 细胞反应消除肿瘤块

核酸疫苗通过强大且特异性的 T 细胞反应，在癌症治疗方面显示出有希望的效力和功效。提高递送抗原的免疫原性有助于延长治疗效果并减少剂量依赖性毒性。在这里，我们系统地评估了趋化因子融合的 HPV16 E6/E7 抗原，以改善核苷酸疫苗在体内诱导的细胞和体液免疫反应。我们发现与不同趋化因子的融合改变了针对抗原的免疫反应的性质。尽管许多趋化因子能够单独或同时放大特定的 CD8 + T 细胞或体液反应。CCL11 被认为是提高免疫原性、促进特异性 CD8 + T 细胞干性和产生肿瘤排斥的最有效趋化因子。将 CCL11 与 E6/E7 抗原融合作为治疗性 DNA 疫苗显着提高了治疗效果，并消除了 92% 荷瘤小鼠 (n = 25) 中已形成的大肿瘤。与CCL11的融合抗原扩大了特异性T细胞的TCR多样性，并诱导活化的特异性T细胞、中性粒细胞、巨噬细胞和树突状细胞（DC）浸润到肿瘤中，从而创建了对肿瘤致命的综合免疫微环境。DNA疫苗与抗CTLA4治疗的结合进一步增强了治疗效果。此外，CCL11还可用于mRNA疫苗设计。总而言之，CCL11 可能是一种有效的抗癌 T 细胞增强剂。